Syndecan-1 regulates dendritic cell migration in cutaneous hypersensitivity to haptens
Syndecan-1 regulates dendritic cell migration in cutaneous hypersensitivity to haptens
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DOI：
10.1111/exd.13374
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发表时间：
2017-11-01
影响因子：
3.6
通讯作者：
Polte, Tobias
中科院分区：
文献类型：
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作者：
Averbeck, Marco;Kuhn, Stephanie;Polte, Tobias
在人类树突状细胞（DC），我们以前在体外证明，syndecan-1（SDC 1）在成熟过程中下调与增强的运动性。我们研究了SDC 1对TNCB（2，4，6-三硝基-1-氯苯）诱导的小鼠皮肤过敏反应（CHS）中DC迁移的影响。我们发现，DC在SDC 1缺陷小鼠迁移速度更快，并以更高的速度淋巴结引流半抗原涂皮肤。SDC 1缺陷半抗原和荧光染料标记的DC连续转移到野生型（WT）小鼠中导致DC向副皮质淋巴结的迁移增加和更快，并且与WT DC相比具有更强的CHS。在SDC 1-/-小鼠中，CCR 7在前15分钟成熟（LPS诱导成熟后）内在DC表面保持更长时间。此外，在SDC 1-/- DC的成熟过程中，发现CCL 2、CCL 3、VCAM 1和talin的时间依赖性上调。然而，SDC 1缺陷型DC的T细胞刺激能力与WT DC相比没有差异。从机制上讲，SDC 1缺陷型DC表现出向CCL 21和CCL 19迁移的增强。这可能是由于SDC 1-/- DC中CCR 7的功能性过表达所致。功能完整的SDC 1缺陷型DC的迁移增加和加速导致CHS恶化。根据我们的研究结果，我们得出结论，DC上的SDC 1负调控DC迁移。
In human dendritic cells (DCs), we previously demonstrated in vitro that syndecan-1 (SDC1) is downregulated during maturation correlating with enhanced motility. We investigated the effects of SDC1 on DC migration in vivo during TNCB(2,4,6-trinitro-1-chlorobenzene)-induced cutaneous hypersensitivity reaction (CHS) in mice. We show that DC in SDC1-deficient mice migrated faster and at a higher rate to lymph nodes draining the hapten-painted skin. Adoptive transfer of SDC1-deficient hapten- and fluorochrome-labelled DC into wild-type (WT) mice led to increased and faster migration of DC to paracortical lymph nodes, and to a stronger CHS compared to WT DC. In SDC1-/- mice, CCR7 remains longer on the DC surface within the first 15-minutes maturation (after LPS-induced maturation). In addition, a time-dependent upregulation of CCL2, CCL3, VCAM1 and talin was found during maturation in SDC1-/- DC. However, no difference in T-cell-stimulating capacity of SDC1-deficient DC was found compared to WT DC. Mechanistically, SDC1-deficient DC showed enhanced migration towards CCL21 and CCL19. This may result from functional overexpression of CCR7 in SDC1-/- DC. Increased and accelerated migration of otherwise functionally intact SDC1-deficient DC leads to an exacerbated CHS. Based on our results, we conclude that SDC1 on DC negatively regulates DC migration.